Developmental regulation of spine motility in the mammalian central nervous system.

The function of dendritic spines, postsynaptic sites of excitatory input in the mammalian central nervous system (CNS), is still not well understood. Although changes in spine morphology may mediate synaptic plasticity, the extent of basal spine motility and its regulation and function remains controversial. We investigated spine motility in three principal neurons of the mouse CNS: cerebellar Purkinje cells, and cortical and hippocampal pyramidal neurons. Motility was assayed with time-lapse imaging by using two-photon microscopy of green fluorescent protein-labeled neurons in acute and cultured slices. In all three cell types, dendritic protrusions (filopodia and spines) were highly dynamic, exhibiting a diversity of morphological rearrangements over short (<1-min) time courses. The incidence of spine motility declined during postnatal maturation, but dynamic changes were still apparent in many spines in late-postnatal neurons. Although blockade or induction of neuronal activity did not affect spine motility, disruption of actin polymerization did. We hypothesize that this basal motility of dendritic protrusions is intrinsic to the neuron and underlies the heightened plasticity found in developing CNS.

[1]  K. Harris,et al.  Slices Have More Synapses than Perfusion-Fixed Hippocampus from both Young and Mature Rats , 1999, The Journal of Neuroscience.

[2]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[3]  John E. Lisman,et al.  A Role of Actin Filament in Synaptic Transmission and Long-Term Potentiation , 1999, The Journal of Neuroscience.

[4]  T. Bliss,et al.  Persistence of individual dendritic spines in living brain slices , 1992, Neuroreport.

[5]  D. Rusakov,et al.  Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  M. Segal,et al.  Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  Masahiko Watanabe,et al.  Diversity Revealed by a Novel Family of Cadherins Expressed in Neurons at a Synaptic Complex , 1998, Neuron.

[8]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[9]  Marco Capogna,et al.  Miniature synaptic events maintain dendritic spines via AMPA receptor activation , 1999, Nature Neuroscience.

[10]  P. Strata,et al.  Control of spine formation by electrical activity in the adult rat cerebellum. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Christian Rosenmund,et al.  Calcium-induced actin depolymerization reduces NMDA channel activity , 1993, Neuron.

[12]  M. Fischer,et al.  Rapid Actin-Based Plasticity in Dendritic Spines , 1998, Neuron.

[13]  H. Eng,et al.  Synthesis of β-Tubulin, Actin, and Other Proteins in Axons of Sympathetic Neurons in Compartmented Cultures , 1999, The Journal of Neuroscience.

[14]  S. B. Kater,et al.  Independent regulation of calcium revealed by imaging dendritic spines , 1991, Nature.

[15]  A. Matus,et al.  High actin concentrations in brain dendritic spines and postsynaptic densities. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Stephen J. Smith,et al.  Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation , 1996, Neuron.

[17]  N. Heintz,et al.  A strategy for the analysis of gene expression during neural development. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Carol A. Mason,et al.  TrkB Signaling Modulates Spine Density and Morphology Independent of Dendrite Structure in Cultured Neonatal Purkinje Cells , 1998, The Journal of Neuroscience.

[19]  F. Engert,et al.  Dendritic spine changes associated with hippocampal long-term synaptic plasticity , 1999, Nature.

[20]  Michael P. Stryker,et al.  Anatomical Correlates of Functional Plasticity in Mouse Visual Cortex , 1999, The Journal of Neuroscience.

[21]  W. Denk,et al.  Dendritic spines as basic functional units of neuronal integration , 1995, Nature.

[22]  S. Kaech,et al.  Volatile anesthetics block actin-based motility in dendritic spines. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Fifková,et al.  Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity , 1982, The Journal of cell biology.

[24]  Stephen J. Smith,et al.  The Dynamics of Dendritic Structure in Developing Hippocampal Slices , 1996, The Journal of Neuroscience.

[25]  B. Mcewen,et al.  Estradiol regulates hippocampal dendritic spine density via an N-methyl- D-aspartate receptor-dependent mechanism , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  F. Crick Do dendritic spines twitch? , 1982, Trends in Neurosciences.

[27]  S. B. Kater,et al.  Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. , 1994, Annual review of neuroscience.

[28]  J. Connor,et al.  Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses , 1991, Nature.

[29]  K. Svoboda,et al.  Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. , 1999, Science.

[30]  J. Wickens Electrically coupled but chemically isolated synapses: Dendritic spines and calcium in a rule for synaptic modification , 1988, Progress in Neurobiology.

[31]  C. Koch,et al.  The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  C. Mason,et al.  Cell-cell interactions influence survival and differentiation of purified purkinje cells in vitro , 1994, Neuron.

[33]  L. C. Katz,et al.  Destabilization of Cortical Dendrites and Spines by BDNF , 1999, Neuron.

[34]  A. Craig,et al.  Role of Actin in Anchoring Postsynaptic Receptors in Cultured Hippocampal Neurons: Differential Attachment of NMDA versus AMPA Receptors , 1998, The Journal of Neuroscience.

[35]  R. Tsien,et al.  Variability of Neurotransmitter Concentration and Nonsaturation of Postsynaptic AMPA Receptors at Synapses in Hippocampal Cultures and Slices , 1999, Neuron.

[36]  J. Fiala,et al.  Synaptogenesis Via Dendritic Filopodia in Developing Hippocampal Area CA1 , 1998, The Journal of Neuroscience.